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The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 6 2384-2392
Copyright © 2003 by The Endocrine Society

Hypertension and the Cortisol-Cortisone Shuttle

Marcus Quinkler and Paul M. Stewart

Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, United Kingdom

Address all correspondence and requests for reprints to: Paul M. Stewart, M.D., F.R.C.P., F.Med.Sci., Professor of Medicine, Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, United Kingdom. E-mail: p.m.stewart{at}bham.ac.uk.

11ß-Hydroxysteroid dehydrogenase type 2 (11ß-HSD2) plays a crucial role in converting hormonally active cortisol to inactive cortisone, thereby conferring specificity on the mineralocorticoid receptor. Mutations in the gene encoding 11ß-HSD2 (HSD11B2) account for an inherited form of hypertension, the syndrome of apparent mineralocorticoid excess, in which cortisol induces hypertension and hypokalemia. A similar clinical picture to apparent mineralocorticoid excess occurs after the ingestion of licorice and carbenoxolone, which are competitive inhibitors of 11ß-HSD2. Reduced 11ß-HSD2 activity may explain the increased sodium retention in preeclampsia, renal disease, and liver cirrhosis. Substrate saturation of 11ß-HSD2 occurs in Cushing’s syndrome and explains the mineralocorticoid excess state that characterizes ectopic ACTH syndrome. Polymorphic variability in the HSD11B2 gene in part determines salt sensitivity, a forerunner for adult onset hypertension. Furthermore, reduced placental 11ß-HSD2 expression might underpin the Barker hypothesis, the epidemiological link between reduced birth weight and adult hypertension. At a prereceptor level, 11ß-HSD2 plays a key role in normal physiology in the corticosteroid regulation of sodium homeostasis and pathophysiology of hypertension.

This work was supported by a Deutsche Forschungsgemeinschaft postdoctoral research fellowship grant (QU142/1-1, to M.Q.) and the Medical Research Council (senior clinical fellowship, to P.M.S.).

Abbreviations: AME, Apparent mineralocorticoid excess; 11ß-HSD, 11ß-hydroxysteroid dehydrogenase; icv, intracerebroventricular; MR, mineralocorticoid receptor; THE, tetrahydrocortisone; THF, 5ß-tetrahydrocortisol; UFE, urinary free cortisone; UFF, urinary free cortisol.




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